Molecular mechanisms of FGF-2 inhibitory activity in the osteogenic context of mouse adipose-derived stem cells (mASCs)

Abstract Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, their molecular mechanisms have not been fully elucidated. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into 2 groups, one co-cultured with adipose-derived stem cells, the other growing independently. Between each group, we compared the wound healing rate, fibroblasts’ survival rate, apoptosis rates, mRNA expressions and protein level of Col-1, Col-3, CTGF, P-4-HB. Results: In our research, no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate were found at the baseline. Adipose-derived stem cells strongly suppressed keloid fibroblasts’ proliferative and invasive behavior, but negatively regulated keloid fibroblast apoptosis. The further measurement of key components in keloid formation showed that adipose-derived stem cells upregulated Col-3 and CTGF levels in normal fibroblasts but downregulated protein expression of CTGF and P-4-HB in keloid fibroblasts. Conclusions: Adipose-derived stem cells had the potential to serve as a promising alternative for keloid treatment.

Download Full-text

Crucial lncRNAs associated with adipocyte differentiation from human adipose-derived stem cells based on co-expression and ceRNA network analyses

PeerJ ◽

10.7717/peerj.7544 ◽

2019 ◽

Vol 7 ◽

pp. e7544 ◽

Cited By ~ 5

Author(s):

Kana Chen ◽

Shujie Xie ◽

Wujun Jin

Keyword(s):

Stem Cells ◽

Molecular Mechanisms ◽

Target Genes ◽

Pearson Correlation ◽

Adipogenic Differentiation ◽

Tyrosine Phosphatase ◽

Regulatory Subunit ◽

Adipose Derived Stem Cells ◽

Network Analyses ◽

Cerna Network

Background Injection of adipose-derived stem cells (ASCs) is a promising treatment for facial contour deformities. However, its treatment mechanisms remain largely unknown. The study aimed to explain the molecular mechanisms of adipogenic differentiation from ASCs based on the roles of long noncoding RNAs (lncRNAs). Methods Datasets of mRNA–lncRNA (GSE113253) and miRNA (GSE72429) expression profiling were collected from Gene Expression Omnibus database. The differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) between undifferentiated and adipocyte differentiated human ASCs were identified using the Linear Models for Microarray Data method. DELs related co-expression and competing endogenous RNA (ceRNA) networks were constructed. Protein–protein interaction (PPI) analysis was performed to screen crucial target genes. Results A total of 748 DEGs, 17 DELs and 51 DEMs were identified. A total of 13 DELs and 279 DEGs with Pearson correlation coefficients > 0.9 and p-value < 0.01 were selected to construct the co-expression network. A total of 151 interaction pairs among 112 nodes (10 DEMs; eight DELs; 94 DEGs) were obtained to construct the ceRNA network. By comparing the lncRNAs and mRNAs in two networks, five lncRNAs (SNHG9, LINC02202, UBAC2-AS1, PTCSC3 and myocardial infarction associated transcript (MIAT)) and 32 genes (i.e., such as phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), protein tyrosine phosphatase receptor type B (PTPRB)) were found to be shared. PPI analysis demonstrated PIK3R1 , forkhead box O1 (FOXO1; a transcription factor) and estrogen receptor 1 (ESR1) were hub genes, which could be regulated by the miRNAs that interacted with the above five lncRNAs, such as LINC02202-miR-136-5p-PIK3R1, LINC02202-miR-381-3p-FOXO1 and MIAT-miR-18a-5p-ESR1. LINC02202 also could directly co-express with PIK3R1. Furthermore, PTPRB was predicted to be modulated by co-expression with LINC01119. Conclusion MIAT, LINC02202 and LINC01119 may be potentially important, new lncRNAs associated with adipogenic differentiation of ASCs. They may be involved in adipogenesis by acting as a ceRNA or co-expressing with their targets.

Download Full-text